For centuries, various natural and unnatural compositions and/or compounds have been added to comestible (edible) foods and beverages to improve their taste. Although it has long been known that there are only a few basic types of “tastes,” the biological and biochemical basis of taste perception was poorly understood, and most taste improving or taste modifying agents have been discovered largely by simple trial and error processes.
For example, one of the five known basic tastes is the “savory” or “umami” flavor of monosodium glutamate (“MSG”), synthetic or natural versions of which are often added to foods, often at concentrations on the order of about 0.05 to about 0.5% by weight. Alternatively, MSG is present in and can be added in the form of certain food additives, such as autolyzed yeast extracts (“AYE”) or hydrolyzed vegetable proteins (“HVP”), which are often added to comestible foods and drinks at a concentration from about 0.1 to about 2% by weight. MSG is however known to produce adverse reactions in some people, and MSG comprises significant amounts of undesirable sodium, but very little progress has been made in identifying artificial substitutes for MSG.
It is also known that a few naturally occurring materials can increase or enhance (multiply) the effectiveness of MSG as a savory flavoring agent, so that less MSG is needed for a given flavoring application. For example, the naturally occurring nucleotide
compounds inosine monophosphate (IMP) and guanosine monophosphate (GMP) are known to have a multiplier (“enhancer”) effect on the savory taste of MSG. IMP and GMP can also be present in AYE or HVP food additives, but are difficult and expensive to isolate and purify from natural sources, or synthesize, and hence have limited practical applications. High potency compounds that would substitute for the savory flavor of MSG5 or enhance the effectiveness of any MSG present, so that less MSG could be employed in food compositions, could be of very high value.
In recent years substantial progress has been made in biotechnology in general, and in better understanding the underlying biological and biochemical phenomena of taste perception. For example, taste receptor proteins have been recently identified in mammals which are involved in taste perception. Particularly, two different families of G protein coupled receptors believed to be involved in taste perception, T2Rs and T1Rs, have been identified. (See, e.g., Nelson, et al., Cell (2001) 106(3):381-390; Adler, et al., Cell (2000) 100(6):693-702; Chandrashekar, et al., Cell (2000) 100:703-711; Matsunami, et al., Number (2000) 404:601-604; Li, et al., Proc. Natl. Acad. Sci. USA (2002) 99:4962-4966; Montmayeur, et al., Nature Neuroscience (2001) 4(S):492-498: U.S. Pat. No. 6,462,148; and PCT publications WO 02/06254, WO 00/63166 art, WO 02/064631, and WO 03/001876, and U.S. Patent Publication No. US 2003/0232407 A1).
Whereas the T2R family includes a family of over 25 genes that are involved in bitter taste perception, the T1R5 only includes three members, T1R1, T1R2, and T1R3. (See Li, et al., Proc. Natl. Acad. Sci. USA (2002) 99:4962-4966.) Recently it was disclosed in WO 02/064631 and/or WO 03/001876 that certain T1R members, when co-expressed in suitable mammalian cell lines, assemble to form functional taste receptors. Particularly it was found that co-expression of T1R1 and T1R3 in a suitable host cell results in a functional T1R1/T1R3 savory (“umami”) taste receptor that responds to savory taste stimuli, including MSG.
More recently, certain publications disclosed the discovery and use of certain amide compounds as very high potency umami tastants and/or synergistic enhancers of the “Umami” taste of MSG.
Nevertheless, the current applicants have unexpectedly discovered that, like many other known artificial flavorants, at higher concentrations some of the new high potency compounds can have flavor differences as compared to MSG, such as mouth-watering side-tastes, a flavor “lingering” as compared to MSG, or in some cases a perception of tongue tingling or numbness. While such side tastes can actually be desirable in some food formulations (e.g., hot and spicy sauces), minimization or masking of any side tastes can, in other applications, be desirable. Such side tastes can become noticeable if the high potency savory compounds are not well dispersed within the comestible compositions. Moreover, while the solubility of the newly discovered high potency compounds is often good in aqueous and polar organic media, solubility can be limited in hydrophobic/lipophilic materials such as fats and oils, which are a natural component of many foods. Accordingly, effective formulation of the new high potency savory flavor compounds to achieve optimal human perception of the savory/Umami flavors, while minimizing side tastes, can sometimes be difficult.
However, when a new chemical entity such as new high potency savory compounds ave been discovered that is safe for human use, the original laboratory process by which the compound was first made may not be optimal for the production of commercial quantities. No large scale synthetic procedures for the preparation of the high potency savory tastant compounds N-(2,4-dimethoxybenzyl)-N′-[2-(pyridin-2-yl)ethyl]oxalamide and 2-H-benzo[3,4-d]1,3-dioxolan-5-yl-N-(propylbutyl)-carboxamide have been disclosed in the prior art, and as such, investigation of suitable processes for large scale preparations of the compounds recited above was undertaken.
To this end, the preparation of savory modulating and/or enhancing formulations that can provide a perceptible savory flavor and/or enhance the flavor of MSG, but avoid and/or overcome issues related to side tastes and solubility and can be used in a variety of applications is needed. The compositions and savory flavorant concentrate compositions and methods disclosed herein meet these unexpected complications and complexities.